Table 2.
Summary of TCM treatment of MIRI by regulating necroptosis, autophagy, and pyroptosis in the past five years
| Type | TCM name | Active constituent | Experimental model | Related pathways | Efficacies and mechanisms | References |
|---|---|---|---|---|---|---|
| Necroptosis | Salvia milorrhiza Bunge | Tanshinone I (TI) | Ttert-butyl hydroperoxide (t-BHP)-stimulated H9c2 cells model; myocardial ischemia-reperfusion (MI/R) model | RIP1/RIP3/MLKL and Akt/Nrf2 signaling pathways | Inhibited the expression of p-RIP1, p-RIP3, and p-MLKL, promoted the phosphorylation of Akt, Nrf2, NQO-1, and HO-1, mitigated ROS generation, and reversed MMP loss. Recovered ECG, reversed the counts of WBC, Neu, Lym, and the release of TNF-α and IL-6, and increased SOD level while decreasing MDA level. | [37] |
| Scutellaria baicalensis Georgi (Lamiaceae) | Baicalin, a flavonoid active substance | myocardial ischemia-reperfusion (IR) model | PI3K-AKT-eNOS pathway | Improved cardiac function, decreased the myocardial infarction area, promoted the production of NO and the level of cGMP, suppressed the protein expression of RIP1, RIP3, and p-MLKL to interrupt CMEC necroptosis. | [38] | |
| Autophagy | Scutellarin (SCU) | A flavonoid purified | Acute myocardial I/R injury and anoxia/reoxygenation (A/R)-induced H9c2 injuries model | Akt/mTORC1/NLRP3 signaling pathway | Reduced NLRP3 inflammasome activation, inhibited mTORC1 activity, and increased Akt phosphorylation. | [48] |
| Artemisinin (ARS) | A sesquiterpene lactone compound | The rats I/R injury model | NLRP3 inflammasome pathway | Reduced infarct size, increased p62, decreased CK-MB, LDH, LC3II/I, NLRP3, ASC, cleaved caspase-1, and IL-1β. | [49] | |
| Panax notoginseng | Panax Notoginseng Saponins (PNS) | A rat model of myocardial injury | HIF-1α/BNIP3 pathway | Decreased CK, MDA, LDH, SOD, and ROS, increased mitochondria autophagosome in myocardial cells, increased the expression of LC3 and the ratio of LC3II/LC3I, increased the expression of HIF-1α, BNIP3, Atg5, and Beclin-1. | [50] | |
| Coptidis Rhizoma | Coptisine, a naturally occurring isoquinoline alkaloid | A hypoxia/reoxygenation (H/R)-treated H9c2 cardiomyocyte model | Autophagosome formation | Reduced the protein level of LC3-II, cleaved Caspase-3, Beclin1, and Sirt1. | [51] | |
| Gastrodian, GAS | Model of Hypoxia/Reoxygenation (H/R) | Autophagic flux | Reduced heart infarct size inhibited expression of p62 and increased LC3II, increased the mitochondrial membrane potential of NRCs, activated AMPK phosphorylation, and reduced mTOR phosphorylation. | [52] | ||
| The root of Pueraria lobata (Willd.) | Pueraria lobata (Pur) | Myocardial hypoxia/reoxygenation (H/R) | Akt signaling pathway | Decreased the ratio of LC3-II/LC3-I and the degradation of p62 and increased the level of Akt. | [53] | |
| Puerarin (Pue) | 8-C-β-D-glucopyranosyl-7,4-hydroxy-isoflavone | Myocardial ischemia/reperfusion (MI/R) injury | SIRT1/NF-κB pathway | Reduced myocardial infarct size and CK-MB, decreased the mRNA and protein levels of TNF-α, IL-6, and IL-1β, decreased the protein levels of Ac-NF-κB, NLRP3, cleaved caspase-1, cleaved IL-1β, and cleaved IL-18, and increased the protein level of SIRT1. | [54] | |
| The rhizome of curcuma | Curcumin, curcumin-peptide hydrogel, a polyphenolic compound | Rat | JAK2/STAT3 pathway | Reduced ROS formation and mitochondrial damage, improved cardiac function, inhibited left ventricular dilatation, ventricular remodeling, and collagen synthesis. | [55] | |
| ischemia-reperfusion model | ||||||
| Turmeric plant | Curcumin (Cur), an alcohol-based molecule that exists in an organic solvent | H9c2 cardiomyocytes model | ER stress and the MAPK pathway | Decreased the levels of LDH and MDA and increased the activity of SOD, inhibited the phosphorylation of ERK1/2 and JNK. | [56] | |
| Pyroptosis | The rhizome of Rheum palmatum | Emodin, an anthraquinone derivative | I/R model | TLR4/MyD88/NF-κB/NLRP3 inflammasome pathway | Increased the rate of cell survival and decreased the myocardial infarct size, suppressed the expression of TLR4, MyD88, phospho-IκBα, phospho-NF-κB, and the NLRP3 inflammasome. | [60] |
| Gastrodian, GAS | Cardiac microvascular endothelial cells and myocardial I/R animal model | NLRP3/caspase-1 pathway | Attenuated infarct size and inflammatory cells infiltration and increased capillary formation, reduced IL-1β production, blocked NLRP3-dependent pyroptotic cell death. | [61] | ||
| Luteolin (Lu) | A flavonoid compound | I/R model | Sirt1/TLR4/NLRP3/NF-κB pathway | Decreased LDH, AST and CK-MB, increased the level of Sirt1, and decreased the levels of NLRP3, ASC, Caspase-1, IL-1β, IL-18, TNF-α, TLR4, MyD88, p-NF-κB p65, and p-IκBα. | [62,63] |
RIP3: receptor-interacting protein 3, RIP1: receptor-interacting protein 1, MLKL: mixed lineage kinase domain-like protein, Akt: protein kinase B, HO-1: Heme oxygenase-1, NQO-1: quinone oxidoreduct-ase-1, ECG: electrocardiograph, WBC: white blood cell, Neu: neutrophil, Lym: lymphocyte, IL-6: interleukin-6, NO: nitric oxide, mTORC1: mechanistic target of rapamycin complex 1, P3: NLR family pyrin domain containing 3, CK-MB: creatine kinase-MB, LC3: microtubule-associated protein light chain 3, ASC: apoptosis-associated speck-like protein, HIF-1α: hypoxia-inducible factor 1α, BNIP3: BCL2 interacting protein 3, Atg5: autophagy-related gene-5, NRCs: neonatal rat cardiomyocytes, AMPK: AMP-activated protein kinase, ER: endoplasmic reticulum, MyD88: myeloid differentiation factor 88, AST: aspartate transaminase.